While exploring space for new habitable worlds, a probe belonging to the bio-engineering corporation Life Foundation discovers a comet covered in symbiotic lifeforms. The probe returns to Earth with four samples, but one escapes and causes the ship to crash in Malaysia. The Life Foundation recovers the other three and transports them to their research facility in San Francisco, where they discover that the symbiotes cannot survive without oxygen-breathing hosts, which often fatally reject the symbiosis. Investigative journalist Eddie Brock reads about these human trials in a classified document in the possession of his fiancée Anne Weying, an attorney preparing a lawsuit defense for the Life Foundation. Brock confronts Life Foundation CEO Carlton Drake about the trials, leading to both Brock and Weying losing their jobs. Consequently, Weying ends their relationship.
Six months later, Drake’s symbiosis trials are closer to success, though one of his symbiotes dies due to carelessness. Brock is approached by Dora Skirth, one of Drake’s scientists who disagrees with his methods and wants to expose him. She helps Brock break into the research facility to search for evidence, and he learns that an acquaintance of his, a homeless woman named Maria, is one of the test subjects. Brock attempts to rescue Maria, but the symbiote possessing her transfers to his body without him realizing, leaving her dead. Brock escapes and soon begins displaying strange symptoms. He reaches out to Weying for help, and her new boyfriend, Dr. Dan Lewis, discovers the symbiote on examining Brock. Drake exposes Skirth to the remaining captive symbiote, killing both. This leaves the symbiote inside Brock as the only known surviving specimen.
Drake sends mercenaries to retrieve the symbiote from Brock, but it manifests around his body as a monstrous creature that fights off the attackers. It later introduces itself to Brock as Venom, and explains that the comet is searching for planets where the symbiotes can possess and devour the inhabitants. Venom offers to spare Brock if he helps the symbiotes achieve their goal, and Brock comes to enjoy the superhuman attributes that the symbiote imbues him with. Brock breaks into his old workplace to turn in evidence of Drake’s crimes, but is surrounded by SWAT officers and is forced to transform to escape. Weying witnesses this transformation and takes Brock back to Lewis’s office, where they explain that the symbiote is slowly rotting Brock’s internal organs. Brock notes that the symbiote has two weaknesses: high-pitched noises and fire. Although Venom claims that the organ damage can be prevented, Weying uses an MRI machine to help Brock separate from the symbiote. Brock is then captured by Drake’s men.
Meanwhile, the fourth symbiote, Riot, makes its way from Malaysia to San Francisco by hopping from body to body. It bonds with Drake, who agrees to take Riot in a Life Foundation space probe to collect the rest of the symbiotes and bring them to Earth. Weying reluctantly bonds with Venom so they can free Brock. When Brock and Venom are bonded again, the latter states that he has been convinced to help protect the Earth from his kind through his interactions with Brock, and the pair attempt to stop Riot and Drake with Weying’s help. Venom damages the probe as it takes off, causing it to explode and kill both Riot and Drake. Weying believes Brock is no longer bonded to Venom after this, and that Venom also died in the explosion. However, the pair remain secretly bonded and set out to protect San Francisco by killing criminals.
Brock also returns to journalism, and in a mid-credits scene, he is invited to interview incarcerated serial killer Cletus Kasady, who promises “carnage” when he escapes.